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用于开发局部递药原位方法的和谐生物材料:当前趋势。

Harmonious Biomaterials for Development of In situ Approaches for Locoregional Delivery of Anti-cancer Drugs: Current Trends.

机构信息

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, India.

The International School Bangalore, Karnataka, India.

出版信息

Curr Med Chem. 2020;27(21):3463-3498. doi: 10.2174/1573406415666190621095726.

Abstract

Locoregional drug delivery is a novel approach for the effective delivery of anti-cancer agents as it exposes the tumors to high concentration of drugs. In situ gelling systems have fetched paramount attention in the field of localized cancer chemotherapy due to their targeted delivery, ease of preparation, prolonged or sustained drug release and improved patient compliance. Numerous polymers have been investigated for their properties like swelling along with biodegradation, drug release and physicochemical properties for successful targeting of the drugs at the site of implantation. The polymers such as chitosan, Hyaluronic Acid (HA), poloxamer, Poly Glycolic Lactic Acid (PGLA) and Poly Lactic Acid (PLA) tend to form in situ hydrogels and have been exploited to develop localized delivery vehicles. These formulations are administered in the solution form and on exposure to physiological environment such as temperature, pH or ionic composition they undergo phase conversion into a hydrogel drug depot. The use of in situ gelling approach has provided prospects to increase overall survival and life quality of cancer patient by enhancing the bioavailability of drug to the site of tumor by minimizing the exposure to normal cells and alleviating systemic side effects. Because of its favorable safety profile and clinical benefits, United States Food and Drug Administration (U.S. FDA) has approved polymer based in situ systems for prolonged locoregional activity. This article discusses the rationale for developing in situ systems for targeted delivery of anti-cancer agents with special emphasis on types of polymers used to formulate the in situ system. In situ formulations for locoregional anti-cancer drug delivery that are marketed and are under clinical trials have also been discussed in detail in this article.

摘要

局部药物递送是一种将抗癌药物有效递送至肿瘤部位的新方法,因为它能使肿瘤暴露于高浓度的药物中。原位凝胶系统因其靶向递送、易于制备、延长或持续释放药物以及提高患者顺应性而在局部化疗领域引起了极大的关注。许多聚合物因其具有的特性,如膨胀和生物降解、药物释放以及物理化学特性,而被用于成功靶向植入部位的药物。壳聚糖、透明质酸(HA)、泊洛沙姆、聚丙交酯乙交酯(PGLA)和聚乳酸(PLA)等聚合物倾向于形成原位水凝胶,并被用于开发局部递送载体。这些制剂以溶液形式给药,暴露于生理环境(如温度、pH 值或离子组成)后,它们会经历相转变为水凝胶药物库。原位凝胶方法的使用为增加癌症患者的总生存率和生活质量提供了前景,方法是通过最大限度地减少对正常细胞的暴露并减轻全身副作用来提高药物在肿瘤部位的生物利用度。由于其有利的安全性和临床益处,美国食品和药物管理局(U.S. FDA)已批准基于聚合物的原位系统用于延长局部区域的活性。本文讨论了开发用于靶向递抗癌药物的原位系统的基本原理,特别强调了用于配制原位系统的聚合物类型。本文还详细讨论了已上市和正在临床试验中的局部抗癌药物递送的原位制剂。

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